Haemophilia A is an inherited bleeding disorder caused by deficiency or dysfunction of coagulation factor VIII (FVIII) activity. The clinical manifestation is not on primary haemostasis—formation of the blood clot occurs normally—but the clot is unstable due to a lack of secondary thrombin formation.
Haemophilia A is currently treated by intravenously injection of coagulation factor FVIII which is either isolated from blood or produced recombinantly. Treatment can be either on-demand or prophylactic. Recent published data support that prophylaxis has significant advantages over on-demand treatment. These include reduction in bleeding frequency and lower risk of developing haemophilic arthropathy, both resulting in a better quality of life for the patients. However, while prophylaxis enables a virtually symptom-free life for the patients, it requires frequent injections in a peripheral vein, typically three times a week, which is known to be painful, difficult, and time consuming. In addition, repeated venipuncture is not always possible in young children. Consequently, a product supporting less frequent administration and/or administration via a more convenient and safe route such as e.g. subcutaneous administration, would to a greater extent enable regular prophylactic treatment.
A FVIII antibody having the ability to enhance the activation of wt FVIII is disclosed in US20090297503. This antibody, however, is also shown to impair binding of wt FVIII to vWF. Impairment of FVIII:vWF binding is generally believed to be undesirable as the circulatory half life of Factor VIII is many fold higher upon vWF binding.
There is thus a need in the art for therapies that support infrequent administration and/or is capable of enhancing the activity of endogenous FVIII, and consequently the procoagulant response, in patients suffering from haemophilia A. Patients with endogenous FVIII include haemophilia A patients suffering from the mild to moderate form and a certain fraction of the severe patients.